Drug Combination Therapy for Breast Cancer

(NeoADAPT Trial)

Overseen By Hopkins Breast Trials

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Paclitaxel, Carboplatin, Checkpoint inhibitors

Disqualifiers: Metastatic disease, Inflammatory breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a drug combination for individuals with stage 2 or 3 triple-negative breast cancer. Participants will receive a mix of medications, including paclitaxel and carboplatin (both chemotherapy drugs), and pembrolizumab (an immunotherapy drug), before surgery to shrink tumors. If the initial treatment proves insufficient, additional drugs may be administered before surgery to enhance results. Suitable candidates are those with triple-negative breast cancer who can tolerate standard chemo-immunotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using carboplatin, paclitaxel, and pembrolizumab together is generally safe for patients with early-stage triple-negative breast cancer. In past studies, most patients tolerated this treatment well, and the side effects were usually manageable.

For pembrolizumab, studies have found it effective and safe when added to standard chemotherapy for this cancer type. Common side effects included tiredness and nausea, but these were not severe for most people.

This combination therapy is used in some breast cancer treatments, indicating a certain level of safety. While side effects can occur, they are usually not serious and can be managed with medical help.

Overall, current evidence considers this treatment safe for use in clinical settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about this drug combination therapy for breast cancer because it combines carboplatin, paclitaxel, and pembrolizumab in a novel way. Pembrolizumab is an immunotherapy that enhances the body's immune system to better recognize and attack cancer cells, which is different from traditional chemotherapy that directly kills cancer cells. This combination aims to improve the effectiveness of treatment by not only attacking the tumor with chemotherapy but also boosting the immune response. This dual approach has the potential to provide better outcomes than current standard treatments alone.

What evidence suggests that this drug combination therapy could be effective for breast cancer?

Research shows that a combination of three drugs—carboplatin, paclitaxel, and pembrolizumab—can be promising for treating triple-negative breast cancer (TNBC). Studies have found that this combination leads to a 48% overall response rate, with nearly half of the patients experiencing a reduction or disappearance of their cancer. Pembrolizumab, a type of immunotherapy, has shown encouraging results in early TNBC. In this trial, participants will receive this combination as neoadjuvant therapy, often used as a standard treatment for early-stage TNBC because it effectively shrinks tumors before surgery. These findings suggest that this treatment effectively combats this aggressive form of breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Cesar A Santa-Maria, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals with stage 2 or 3 triple negative breast cancer. Participants will undergo specific chemotherapy and immunotherapy treatments, followed by imaging tests like PET scans and MRI to monitor response. Those showing complete clinical response go straight to surgery; others receive additional chemo before surgery.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My doctor agrees I can handle chemo-immunotherapy without major health risks.

Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria

My cancer has spread or returned in the chest area.

I have been diagnosed with inflammatory breast cancer.

Patients unable to undergo PET or MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive 4 cycles of paclitaxel, carboplatin, and pembrolizumab. PET scan at baseline and after 1 cycle, MRI after treatment completion.

12 weeks

4 visits (in-person)

Surgery

Patients with clinical complete response proceed to surgery. Patients with residual disease may receive additional neoadjuvant therapy before surgery.

4 weeks

1 visit (in-person)

Adjuvant Therapy

Patients with pathologic complete response may receive pembrolizumab. Patients with residual disease may receive additional adjuvant therapy.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview

The study tests a combination of neoadjuvant therapies (paclitaxel, carboplatin, pembrolizumab) in patients with TNBC, using PET scans for early treatment adaptation. It explores whether changing therapy based on PET scan results can improve outcomes before surgery.

How Is the Trial Designed?

Group I: Neoadjuvant therapy Experimental Treatment 7 Interventions

4 cycles of paclitaxel/carboplatin/pembrolizumab

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

Paclitaxel and carboplatin, both effective as single agents for advanced breast cancer, are being evaluated in combination as a first-line chemotherapy treatment, with a phase II trial currently underway.

The combination therapy is noted for its tolerability and a unique platelet-sparing effect, which could be beneficial for patients undergoing treatment, as established in other cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin for advanced breast cancer. Perez, EA., Hartmann, LC.[2015]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 55 women with resectable and locally advanced breast cancer, neoadjuvant treatment with carboplatin and weekly paclitaxel, with or without trastuzumab, resulted in a high pathologic complete response (pCR) rate of 45%, particularly in patients with HER2-positive tumors (76% pCR rate).

The treatment was well tolerated, with no severe side effects like febrile neutropenia, and showed promising recurrence-free survival (RFS) rates of 88.7% at a median follow-up of 28 months, suggesting the regimen's effectiveness and safety in high-risk breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. Sikov, WM., Dizon, DS., Strenger, R., et al.[2022]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

The combination of paclitaxel and carboplatin (PC) has shown promising response rates of 40-60% and median survival times of 12-20 months in patients with advanced breast cancer, making it a viable alternative to traditional anthracycline-based treatments.

In a randomized phase III trial, PC demonstrated equivalent efficacy and manageable toxicity compared to the standard treatment of epirubicin/paclitaxel, suggesting it could be a safer option for patients with prior anthracycline exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. Pentheroudakis, G., Razis, E., Athanassiadis, A., et al.[2018]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Paclitaxel has shown high effectiveness in treating advanced breast cancer, including cases resistant to anthracyclines, prompting research into its combination with anthracyclines like doxorubicin.

Clinical trials of the paclitaxel/doxorubicin combination have reported promising response rates, although the toxicity profiles vary significantly based on the administration schedule used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and doxorubicin in metastatic breast cancer. Gehl, J., Boesgaard, M., Paaske, T., et al.[2015]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10767305/

Phase II Clinical Trial of Pembrolizumab and Chemotherapy ...

An ORR of 48.0%, median PFS and OS of 5.8 and 13.4 months align with outcomes previously described in mTNBC treated with pembrolizumab and chemotherapy. RNA ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1910549

Pembrolizumab for Early Triple-Negative Breast Cancer

Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative ...

3.

keytrudahcp.com

keytrudahcp.com/efficacy/early-stage-triple-negative-breast-cancer/

KEYNOTE-522 - Clinical Trial Results | HCP

Health care professionals may view findings from KEYNOTE-522, a clinical trial for patients with high-risk early-stage triple-negative breast cancer (TNBC).

4.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2812294

Clinical and Biomarker Findings of Neoadjuvant ...

This single-group phase 2 clinical trial including 115 evaluable women with TNBC found that neoadjuvant pembrolizumab plus carboplatin and docetaxel showed an ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949820124000390

Real-world safety and effectiveness of neoadjuvant ...

Neoadjuvant chemotherapy (NAC) with the addition of pembrolizumab has become the standard of care for early-stage II-III triple-negative breast cancer (TNBC).

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40233520/

Real-world evidence of the efficacy of neoadjuvant ...

Neoadjuvant pembrolizumab has shown efficacy in improving pathologic complete response (pCR) rates and survival outcomes in triple-negative breast cancer (TNBC ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06492759

High Dose Radiation Therapy With Pembrolizumab and ...

This phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works ...